Korean Journal of Clinical Laboratory Science (대한임상검사과학회지)

Korean Society for Clinical Laboratory Science (대한임상검사과학회)
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Menadione Induced Apoptosis in MKN45 Cells via Down-regulation of Survivin

Menadione의 Survivin 하향 조절을 통한 MKN45 세포의 세포사멸 유도 효과

  • Lee, Min Ho (Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University) ;
  • Kim, Jeongyong (Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University) ;
  • Cho, Yoonjung (Forensic DNA Division, National Forensic Service) ;
  • Kim, Do Hyun (Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University) ;
  • Yang, Ji Yeong (Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University) ;
  • Kwon, Hye Jin (Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University) ;
  • Park, Min (Department of Biomedical Laboratory Science, Daekyeung University) ;
  • Woo, Hyun Jun (Department of Clinical Laboratory Science, College of Medical Sciences, Daegu Haany University) ;
  • Kim, Sa-Hyun (Department of Clinical Laboratory Science, Semyung University) ;
  • Kim, Jong-Bae (Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University)
  • 이민호 (연세대학교 보건과학대학 임상병리학과) ;
  • 김정용 (연세대학교 보건과학대학 임상병리학과) ;
  • 조윤정 (국립과학수사연구원 법유전자과) ;
  • 김도현 (연세대학교 보건과학대학 임상병리학과) ;
  • 양지영 (연세대학교 보건과학대학 임상병리학과) ;
  • 권혜진 (연세대학교 보건과학대학 임상병리학과) ;
  • 박민 (대경대학교 임상병리학과) ;
  • 우현준 (대구한의대학교 의과학대학 임상병리학과) ;
  • 김사현 (세명대학교 임상병리학과) ;
  • 김종배 (연세대학교 보건과학대학 임상병리학과)
  • Received : 2018.11.08
  • Accepted : 2018.11.29
  • Published : 2019.03.31
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Abstract

Menadione is known as an anti-tumor factor. Many studies have reported the potential anti-cancer role of menadione against a range of cancer cell lines. In this study, the anti-cancer effects of menadione and the underlying molecular signaling involved in apoptosis was investigated in gastric cancer cell lines. The menadione treatment decreased the cell viability of MKN45 gastric cancer cells. The decreased cell viability was attributed to the induction of apoptosis, which was confirmed by the results indicating the activation of caspase-3 and -7 and the cleavage of PARP in Western blotting. The upstream regulatory molecules involved in apoptosis were investigated further and it was discovered that menadione reduced the expression of survivin, an inhibitor of upstream apoptosis proteins. In addition, a transcription factor ${\beta}$-catenin, which is known to regulate survivin expression, was down-regulated by menadione. A previous report showed that menadione inhibited XIAP expression to induce apoptosis and induced G2/M cell cycle arrest in AGS cells. This study elucidated another inhibitory mechanism of menadione against gastric cancer cells in a different cell line. Although further studies will be needed, the inhibitory mechanism demonstrated in this study will help better understand the anti-cancer effects of menadione.

Menadione은 종양 억제 물질로 알려진 바 있다. 현재 많은 연구에서 다양한 암세포주에 대하여 Menadione의 잠재적인 항암물질로서의 가능성이 보고되었다. 본 연구에서는 Menadione의 항암효과와 세포사멸작용에 연관된 분자신호를 위암세포주에서 확인하였다. Menadione 처리는 위암세포인 MKN45의 세포생존능을 감소시켰다. 감소된 세포생존능은 Western blotting을 통해 caspase-3 과 caspase-7의 활성화와 PARP가 cleavage 된 것을 확인함으로써 세포사멸작용이 유도되었다는 것을 확인했다. 위세포사멸단백질들의 저해제로 작용하는 survivin의 발현을 menadione이 억제한다는 것을 확인함으로써, 세포사멸과정에 포함된 상위조절인자를 확인했다. 우리는 survivin 발현을 조절하는 전사인자로 알려진 ${\beta}$-catenin 또한 menadione에 의해 하향 조절된다는 것을 확인했다. 이전 연구에서 우리는 menadione이 세포사멸유도를 저해는 XIAP의 발현을 억제한다는 것을 확인했으며, menadione이 AGS세포에서 G2/M 세포주기 정체를 유도한다는 것을 확인하였다. 우리는 또 다른 위암세포주인 MKM45 세포에서 menadione의 이전과 다른 항암 기전을 밝혀냈다. 비록 더 자세한 연구가 필요하겠지만, 이 연구를 통해 증명된 억제기전은 menadione에 의한 항암효과를 이해하는 데 도움이 될 것으로 사료된다.

Keywords

References

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